Identification of Key Genes Associated with Tumor Microenvironment Infiltration and Survival in Gastric Adenocarcinoma via Bioinformatics Analysis
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Microarray Data
2.2. Identification of DEGs between Normal and GC Tissue
2.3. Functional Enrichment Analyses of the GC-Related DEGs
2.4. Construction of PPI Network and Identification of Hub DEGs
2.5. Prognostic Value of Hub DEGs as Biomarkers in GC
2.6. Correlation Analyses between Hub DEGs and Infiltrating Immune Cells
2.7. Expression of Hub Genes in Normal or GC Tissue
3. Results
3.1. Identification of DEGs between Normal and GC Tissue
3.2. Functional Enrichment Analyses
3.3. Construction of PPI Network and Identification of Hub DEGs
3.4. Survival Analysis of Hub DEGs in GC
3.5. TME Evaluation in GC
4. Discussion
5. Conclusions and Limitations
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
BPs | Biological Processes |
CAFs | Cancer-associated Fibroblasts |
CCs | Cellular Components |
DEGs | Differentially Expressed Genes |
ECM | Extracellular Matrix |
ECX | Epirubicin, Cisplatin, and Capecitabine |
EMR | Endoscopic Mucosal Resection |
ESD | Endoscopic Submucosal Dissection |
FDA | Food and Drug Administration |
FLOT | Fluorouracil, Oxaliplatin, Docetaxel, and Leucovorin |
GC | Gastric Cancer/Gastric Carcinoma |
GEO | Gene Expression Omnibus |
GO | Gene Ontology |
KEGG | Kyoto Encyclopedia of Genes and Genomes |
MDSCs | Myeloid-derived Suppressor Cells |
MFs | Molecular Functions |
NFs | Normal Fibroblasts |
PD-L1 | Programmed Death-ligand 1 |
PPI | Protein–Protein Interaction |
TAMs | Tumor-associated Macrophages |
TIMER | Tumor Immune Evaluation Resource |
TME | Tumor Microenvironment |
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(a) | ||||||||
---|---|---|---|---|---|---|---|---|
ID | Term_Description | Fold_Enrichment | Occurrence | Support | Lowest_p | Highest_p | Up_Regulated | |
1 | GO:0030199 | collagen fibril organization | 50.540767 | 10 | 0.065658240 | 5.736930e-08 | 5.736930e-08 | BMP1, COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, ADAMTS2 |
2 | GO:0043588 | skin development | 41.876636 | 10 | 0.025253169 | 2.297293e-05 | 2.297293e-05 | COL3A1, COL5A1, COL5A2 |
3 | GO:0035987 | endodermal cell differentiation | 32.212797 | 10 | 0.030456853 | 4.686940e-05 | 4.686940e-05 | COL8A1, COL12A1, FN1, INHBA |
4 | GO:0031175 | neuron projection development | 8.488507 | 10 | 0.010101268 | 1.162934e-03 | 1.162934e-03 | APOE, MYOC, SH3GL2 |
5 | GO:0001501 | skeletal system development | 22.334206 | 10 | 0.005050634 | 2.114611e-03 | 2.114611e-03 | COL1A1, COL1A2, COL10A1, FBN1, HOXA13, TNFRSF11B, SOX4, TEAD4 |
6 | GO:0003215 | cardiac right ventricle morphogenesis | 38.069669 | 10 | 0.012719036 | 2.225033e-03 | 5.559604e-03 | GATA4, SOX4 |
7 | GO:0016567 | protein ubiquitination | 2.448926 | 10 | 0.010101268 | 2.942256e-03 | 2.942256e-03 | NFE2L2, KLHL25 |
8 | GO:2001234 | negative regulation of apoptotic signaling pathway | 14.955941 | 10 | 0.005050634 | 3.680761e-03 | 3.680761e-03 | GATA4 |
9 | GO:0033700 | phospholipid efflux | 38.069669 | 10 | 0.005050634 | 3.707395e-03 | 3.707395e-03 | APOC1, APOE |
10 | GO:0001568 | blood vessel development | 27.917757 | 10 | 0.025253169 | 4.246779e-03 | 4.246779e-03 | COL1A1, COL1A2 |
(b) | ||||||||
1 | GO:0005788 | endoplasmic reticulum lumen | 13.232394 | 10 | 0.180195851 | 9.961557e-11 | 9.961557e-11 | APOE, SERPINH1, COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, COL6A3, COL8A1, COL10A1, COL12A1, FBN1, FN1, IGFBP4, SPP1, TIMP1, P4HA3 |
2 | GO:0062023 | collagen-containing extracellular matrix | 18.207233 | 10 | 0.085860776 | 2.192636e-08 | 2.192636e-08 | BGN, COL1A1, COL3A1, COL5A1, COL6A3, FN1, MYOC, SFRP2 |
3 | GO:0031012 | extracellular matrix | 22.274806 | 10 | 0.095477387 | 1.306355e-05 | 1.306355e-05 | APOE, COL6A3, ELN, FBN1, FN1 |
4 | GO:0005793 | endoplasmic reticulum–Golgi intermediate compartment | 8.546252 | 10 | 0.050761421 | 1.484223e-05 | 7.398274e-05 | SERPINH1, FN1 |
5 | GO:0001527 | microfibril | 34.897196 | 10 | 0.015267274 | 5.961104e-04 | 9.932217e-04 | FBN1, MFAP2 |
6 | GO:0070062 | extracellular exosome | 3.579200 | 10 | 0.010101268 | 1.037442e-03 | 1.037442e-03 | APOE, FN1 |
7 | GO:0034361 | very-low-density lipoprotein particle | 29.911883 | 10 | 0.005050634 | 1.369197e-03 | 1.369197e-03 | APOC1, APOE |
8 | GO:0071682 | endocytic vesicle lumen | 23.264798 | 10 | 0.010050251 | 1.381399e-03 | 6.434259e-03 | APOE, SPARC |
9 | GO:0034364 | high-density lipoprotein particle | 27.917757 | 10 | 0.005050634 | 1.579702e-03 | 1.579702e-03 | APOC1, APOE |
10 | GO:0031463 | Cul3-RING ubiquitin ligase complex | 6.158329 | 10 | 0.010101268 | 5.060305e-03 | 5.060305e-03 | KLHL25 |
(c) | ||||||||
1 | GO:0048407 | platelet-derived growth factor binding | 76.139337 | 10 | 0.055556973 | 2.976699e-14 | 2.976699e-14 | COL1A1, COL1A2, COL3A1, COL5A1 |
2 | GO:0005201 | extracellular matrix structural constituent | 36.949973 | 10 | 0.106063311 | 6.443542e-06 | 6.443542e-06 | COL3A1, ELN, FBN1, FN1, MUC5AC, NID2 |
3 | GO:0002020 | protease binding | 12.316658 | 10 | 0.085860776 | 9.474422e-05 | 1.288232e-04 | COL1A1, COL1A2, COL3A1, FAP, FN1 |
4 | GO:0005178 | integrin binding | 15.592364 | 10 | 0.025253169 | 1.422341e-04 | 1.440477e-04 | COL3A1, FAP, FBN1, FN1, SFRP2, SPP1, THY1 |
5 | GO:0000976 | transcription cis-regulatory region binding | 3.172472 | 10 | 0.010101268 | 6.020621e-04 | 6.733792e-03 | GATA4, NFE2L2, SOX4 |
6 | GO:0048156 | tau protein binding | 16.106398 | 10 | 0.010101268 | 1.568042e-03 | 1.568042e-03 | APOE |
7 | GO:0043395 | heparan sulfate proteoglycan binding | 17.448598 | 10 | 0.005050634 | 1.989792e-03 | 1.989792e-03 | APOE |
8 | GO:0043394 | proteoglycan binding | 32.212797 | 10 | 0.025253169 | 2.351293e-03 | 2.351293e-03 | COL5A1, FN1 |
9 | GO:0030020 | extracellular matrix structural constituent conferring tensile strength | 41.876636 | 10 | 0.005050634 | 2.531860e-03 | 2.531860e-03 | COL1A1, COL6A3 |
10 | GO:0001968 | fibronectin binding | 19.941255 | 10 | 0.005050634 | 2.532614e-03 | 2.532614e-03 | MYOC, SFRP2 |
(d) | ||||||||
1 | hsa04974 | protein digestion and absorption | 21.149816 | 10 | 0.100502513 | 5.555187e-11 | 5.555187e-11 | ELN, COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, COL6A3, COL8A1, COL10A1, COL12A1 |
2 | hsa04512 | ECM–receptor interaction | 14.276126 | 10 | 0.061069098 | 1.036954e-06 | 1.036954e-06 | COL1A1, COL1A2, COL6A3, THBS2, FN1, SPP1 |
3 | hsa04510 | focal adhesion | 8.502870 | 10 | 0.035354437 | 2.685352e-05 | 2.685352e-05 | COL1A1, COL1A2, COL6A3, THBS2, FN1, SPP1, PGF, TLN2 |
4 | hsa04611 | platelet activation | 8.581278 | 10 | 0.010101268 | 1.964620e-04 | 1.964620e-04 | TLN2, COL1A1, COL1A2, COL3A1, PLA2G4C |
5 | hsa05205 | proteoglycans in cancer | 3.094333 | 10 | 0.015151902 | 2.490706e-04 | 2.490706e-04 | COL1A1, COL1A2, FN1 |
6 | hsa04933 | AGE-RAGE signaling pathway in diabetic complications | 8.459926 | 10 | 0.055556973 | 5.189137e-04 | 5.189137e-04 | FN1, COL1A1, COL1A2, COL3A1 |
7 | hsa05146 | amoebiasis | 8.292403 | 10 | 0.055556973 | 5.512279e-04 | 5.512279e-04 | COL1A1, COL1A2, FN1, COL3A1 |
8 | hsa05415 | diabetic cardiomyopathy | 3.323543 | 10 | 0.010101268 | 7.352484e-04 | 7.352484e-04 | COL1A1, COL1A2, COL3A1 |
9 | hsa04926 | relaxin signaling pathway | 4.907418 | 10 | 0.010101268 | 1.126101e-03 | 1.126101e-03 | COL1A1, COL1A2, COL3A1 |
10 | hsa04310 | Wnt signaling pathway | 2.507583 | 10 | 0.005050634 | 1.259368e-03 | 1.259368e-03 | SFRP2, SFRP4 |
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Konstantis, G.; Tsaousi, G.; Pourzitaki, C.; Kasper-Virchow, S.; Zaun, G.; Kitsikidou, E.; Passenberg, M.; Tseriotis, V.S.; Willuweit, K.; Schmidt, H.H.; et al. Identification of Key Genes Associated with Tumor Microenvironment Infiltration and Survival in Gastric Adenocarcinoma via Bioinformatics Analysis. Cancers 2024, 16, 1280. https://doi.org/10.3390/cancers16071280
Konstantis G, Tsaousi G, Pourzitaki C, Kasper-Virchow S, Zaun G, Kitsikidou E, Passenberg M, Tseriotis VS, Willuweit K, Schmidt HH, et al. Identification of Key Genes Associated with Tumor Microenvironment Infiltration and Survival in Gastric Adenocarcinoma via Bioinformatics Analysis. Cancers. 2024; 16(7):1280. https://doi.org/10.3390/cancers16071280
Chicago/Turabian StyleKonstantis, Georgios, Georgia Tsaousi, Chryssa Pourzitaki, Stefan Kasper-Virchow, Gregor Zaun, Elisavet Kitsikidou, Moritz Passenberg, Vasilis Spyridon Tseriotis, Katharina Willuweit, Hartmut H. Schmidt, and et al. 2024. "Identification of Key Genes Associated with Tumor Microenvironment Infiltration and Survival in Gastric Adenocarcinoma via Bioinformatics Analysis" Cancers 16, no. 7: 1280. https://doi.org/10.3390/cancers16071280
APA StyleKonstantis, G., Tsaousi, G., Pourzitaki, C., Kasper-Virchow, S., Zaun, G., Kitsikidou, E., Passenberg, M., Tseriotis, V. S., Willuweit, K., Schmidt, H. H., & Rashidi-Alavijeh, J. (2024). Identification of Key Genes Associated with Tumor Microenvironment Infiltration and Survival in Gastric Adenocarcinoma via Bioinformatics Analysis. Cancers, 16(7), 1280. https://doi.org/10.3390/cancers16071280